a study to assess the safety and tolerability of nusinersen (isis 396443) in participants with spinal muscular atrophy (sma).

Conditions: Spinal Muscular Atrophy

Summary: the primary objective of part 1 of this study is to assess the safety and tolerability of nusinersen in participants with sma who are not eligible to participate in the clinical studies isis 396443-cs3b (nct02193074) or isis 396443-cs4 (nct02292537). the secondary objective of part 1 of this study is to examine the pharmacokinetics (pk) of nusinersen in participants with sma. the primary objective of part 2 of this study is to assess the long-term safety and tolerability of nusinersen in participants with sma who participated in part 1 and completed their end of part 1 evaluation assessments. the secondary objective of part 2 of this study is to examine the pk of nusinersen in participants with sma who participated in part 1 and completed their end of part 1 evaluation assessments.

part 2 is an open label extension phase.

Eligibility criteria:
key inclusion criteria: * genetic documentation of 5q sma homozygous gene deletion, mutation, or compound heterozygote. * onset of clinical signs and symptoms consistent with sma at ≤6 months of age and have documentation of 3 smn2 copies or onset of clinical signs and symptoms consistent with sma at ≤6 months of age, \>7 months of age (211 days) at screening, and have documentation of 2 smn2 copies or onset of clinical signs and symptoms consistent with sma at \>6 months of age, are ≤18 months of age at screening, and have documentation of 2 or 3 smn2 copies. * meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedures. * medical care, such as routine immunizations meets and is expected to continue to meet guidelines set out in the consensus statement for standard of care in sma, in the opinion of the investigator. * participants with 2 smn2 copies must reside within approximately 9 hours' ground-travel distance from a participating study site for the duration of the study. key exclusion criteria: * meets additional study related criteria. * any previous exposure to isis 396443; previous dosing in this study or previous studies with isis 396443. * signs or symptoms of sma present at birth or within the first week after birth. * ventilation for ≥16 hours per day continuously for \>21 days at screening. * permanent tracheostomy, implanted shunt for csf drainage, or implanted central nervous system (cns) catheter at screening. * history of brain or spinal cord disease that would interfere with the lp procedure, csf circulation, or safety assessments. * hospitalization for surgery (e.g., scoliosis surgery), pulmonary event, or nutritional support within 2 months prior to screening, or hospitalization for surgery planned during the study. * clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ecg), as assessed by the investigator. * treatment with an investigational drug for sma (e.g., albuterol/salbutamol, riluzole, carnitine, sodium phenylbutyrate, valproate, hydroxyurea), biological agent, or device within 30 days prior to screening. any history of gene therapy, prior antisense oligonucleotide (aso) treatment, or cell transplantation. for part 2 only: to be eligible to participate in part 2 of this study, participants must meet the following eligibility criteria at the time of consent to participate in part 2: participation in part 1 and completion of the end of part 1 evaluation assessments. ability of parent(s) or legal guardian(s) to understand the purpose and risks of the study and to provide signed and dated informed consent on the part 2 informed consent form (icf) and authorization to use confidential health information in accordance with national and local participant privacy regulations. able to complete all study procedures, measurements, and visits, and parent or legal guardian/participant has adequately supportive psychosocial circumstances, in the opinion of the investigator. participants will be excluded from the part 2 if they meet the following exclusion criterion at the time of consent into part 2 of the study: any significant change in clinical status, including laboratory tests that, in the opinion of the investigator, would make them unsuitable to participate in part 2. the investigator must reassess the subject's medical fitness for participation and consider any diseases that would preclude treatment. note: other protocol defined inclusion/exclusion criteria may apply.

Keywords: embrace sma